复发转移性胃癌患者HER2基因扩增、蛋白表达及预后的关系

Comparison of HER2 gene amplification and protein expression in recurrent / metastatic gastric cancer and its correlation with prognosis

目的探讨复发转移性胃癌肿瘤原发灶HER2基因扩增与蛋白表达的相关性,及与临床病理特征和预后的关系。方法收集237例复发转移性胃或胃食管交界处腺癌肿瘤原发灶标本,分别应用荧光原位杂交法(FISH)和免疫组织化学法(IHC)检测HER2基因扩增和蛋白的表达。结果 FISH检测HER2基因扩增18.1%(43/237);IHC检测HER2蛋白表达-、1+、2+、3+分别为160例(67.5%)、34例(14.3%)、17例(7.2%)和26例(11.0%)。HER2总体阳性率(FISH+或IHC 3+)为19.0%(45/237)。FISH与IHC方法总的符合率较好,达92.4%(219/237),呈显著正相关(r=0.696,P<0.01)。HER2更常见于胃食管交界处腺癌、肠型胃癌及分化较好的胃癌。胃癌HER2阳性表达与肝、肺等广泛的转移相关。对215例接受全身化疗的患者进行生存分析显示,HER2阳性状态与较差的生存时间相关。结论胃癌HER2基因扩增及蛋白表达具有较好的一致性。胃癌HER2的表达与预后差相关。

Objective To investigate HER2 gene amplification and protein expression in patients with advanced gastric or gastroesophageal cancer（ GC / GEC） and its relation to clinicopathological features and prognosis of patients.Methods Tumor tissue samples from 237 patients with recurrent / metastatic GC / GEC were collected. HER2 gene amplification was detected by fluorescence in situ hybridization（ FISH） and protein over-expression was determined by immunohistochemistry（ IHC）. The relation of HER2 status with clinicopathological parameters and overall survival of patients was analyzed. Results FISH showed that 18. 1%（ 43 /237） of gastric cancer tissue samples displayed HER2 gene amplification; IHC revealed that-,1 ＋,2 ＋,and 3 ＋ HER2 protein expressions were displayed in 160（ 67. 5%）,34（ 14. 3%）,17（ 7. 2%） and 26（ 11. 0%） cases of gastric cancer,respectively. The total HER2 positive rate（ FISH ＋ /IHC3 ＋） was 19. 0%（ 45 /237）. There was a significant correlation between HER2 FISH and IHC results. The whole concordance rate was 92. 4%（ 219 /237,r = 0. 696,P〈0. 01）. HER2 positivity was closely associated with primary tumor location（ GEC）,histological subtype（ intestinal diffuse）,tumor grade（ well-differentiated）,and extensive liver and lung metastasis（ all P〈0. 05）. Survival analysis of 215 patients who received systemic chemotherapy showed that HER2 positive status was significantly correlated with worse overall survival. Conclusion The HER2 FISH and IHC results are closely correlated in gastric cancer. HER2 positivity is associated with liver and lung metastasis and poor overall survival.